In the present study, we showed that lactate mediated H3K18lac to promote the expression of HMGB1 in endometriosis, and HMGB1 knockdown significantly decreased the cell viability, migration, and invasion of the lactate-treated nESCs; besides, lactate induced the expression of HMGB1 and increased the phosphorylation of AKT and the expression of c-MYC and Cyclin D1, all of which could be blocked by HMGB1 silencing. Here, AKT1 is linked to endometriosis.